Heart, Lung and Circulation

Are We There Yet? Exploring the Use of Single-Pill Combination Therapy in the Management of Raised Blood Pressure in Australia

Published:February 24, 2022DOI:


      Single-pill combination (SPC) therapy is recommended as first-line therapy for most patients in global hypertension guidelines due to benefits of improved adherence and blood pressure (BP) control. We aimed to understand factors affecting SPC use in the management of raised BP in Australia.


      A mixed-method study comprising of qualitative (policy review and interviews) and quantitative (Pharmaceutical Benefits Scheme [PBS] data) approaches.

      Main Outcome Measures

      Australian and international hypertension guideline recommendations regarding SPC use; the Australian registration and subsidy approval processes of SPCs; use of SPCs on the PBS; cost-analysis of PBS-listed SPCs compared to free-drug combinations; perceptions of healthcare providers towards SPCs.


      The 2016 Australian Heart Foundation’s “Guideline for the diagnosis and management of hypertension in adults” does not recommend combination therapy (including SPCs) as first-line treatment. Additional challenges in the uptake of SPCs include: (1) the additional PBS requirements and barriers imposed for the listing of SPCs. (2) Script volumes for SPCs have not matched the rise in the number of SPCs listed for subsidy, have plateaued since 2016 and remained significantly lower than single constituent scripts. (3) SPCs are not subsidised by the PBS for initial treatment. Most SPCs provided substantial cost savings for individual patients compared to free-drug combinations. Health care providers were positive about the cost-saving and convenience of SPCs, however perceived negatives included inflexibility of SPCs during dose titration, medicine shortages, and potential adverse effects when initiating treatment with multiple drugs.


      The safety, efficacy and cost-saving potential of SPCs have been established in the literature but several roadblocks in the existing health system in Australia impede uptake. Interventions addressing these barriers may facilitate improved uptake, which may in turn improve blood pressure control in Australia.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Heart, Lung and Circulation
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • World Health Organization
        Guideline for the pharmacological treatment of hypertension in adults.
        World Health Organization, Geneva2021 ([accessed 18.2.22])
        • Australian Institute of Health and Welfare
        Australian burden of disease study: impact and causes of illness and death in Australia in 2015.
        AIHW, Canberra2019 ([accessed 18.2.22])
        • Carnagarin R.
        • Fonseca R.
        • Brockman D.
        • Critchley S.
        • Tan I.
        • Trengove N.
        • et al.
        May Measurement Month 2018: an analysis of blood pressure screening results from Australia.
        Eur Heart J Suppl. 2020; 22: H17-H19
        • National Heart Foundation of Australia
        Guideline for the diagnosis and management of hypertension in adults 2016.
        • Atkins E.R.
        • Chow C.K.
        Low-dose combination therapy for initial treatment of hypertension.
        Curr Hypertens Rep. 2020; 22: 65
        • Verma A.A.
        • Khuu W.
        • Tadrous M.
        • Gomes T.
        • Mamdani M.M.
        Fixed-dose combination antihypertensive medications, adherence, and clinical outcomes: a population-based retrospective cohort study.
        PLoS Med. 2018; 15e1002584
        • Lung T.
        • Jan S.
        • de Silva H.A.
        • Guggilla R.
        • Maulik P.K.
        • Naik N.
        • et al.
        Fixed-combination, low-dose, triple-pill antihypertensive medication versus usual care in patients with mild-to-moderate hypertension in Sri Lanka: a within-trial and modelled economic evaluation of the TRIUMPH trial.
        Lancet Glob Health. 2019; 7: e1359-e1366
        • Benjamin I.J.
        • Kreutz R.
        • Olsen M.H.
        • Schutte A.E.
        • Lopez-Jaramillo P.
        • Frieden T.R.
        • et al.
        Fixed-dose combination antihypertensive medication.
        Lancet. 2019; 394: 637-638
        • Unger T.
        • Borghi C.
        • Charchar F.
        • Khan N.A.
        • Poulter N.R.
        • Prabhakaran D.
        • et al.
        2020 International Society of Hypertension Global Hypertension Practice Guidelines.
        Hypertension. 2020; 75: 1334-1357
        • Williams B.
        • Mancia G.
        • Spiering W.
        • Agabiti Rosei E.
        • Azizi M.
        • Burnier M.
        • et al.
        2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Cardiology and the European Society of Hypertension.
        J Hypertens. 2018; 36: 1953-2041
        • Whelton P.K.
        • Carey R.M.
        • Aronow W.S.
        • Casey Jr., D.E.
        • Collins K.J.
        • Dennison Himmelfarb C.
        • et al.
        2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
        J Am Soc Hypertens. 2018; 12 (579.e1–73)
        • PBS Information Management Section - Pricing and PBS Policy Branch
        PBS Expenditure and Prescriptions Report (1 July 2019 to 30 June 2020).
        Department of Health, Canberra2020 ([accessed 18.2.22])
        • Clarke P.M.
        • Avery A.B.
        Evaluating the costs and benefits of using combination therapies.
        Med J Aust. 2014; 200: 1-3
        • Gadzhanova S.
        • Ilomäki J.
        • Roughead E.E.
        Antihypertensive use before and after initiation of fixed-dose combination products in Australia: a retrospective study.
        Int J Clin Pharm. 2013; 35: 613-620
        • Falster M.O.
        • Buckley N.A.
        • Brieger D.
        • Pearson S.-A.
        Antihypertensive polytherapy in Australia: prevalence of inappropriate combinations, 2013–2018.
        J Hypertens. 2020; 38: 1586-1592
        • Bigdeli M.
        • Jacobs B.
        • Tomson G.
        • Laing R.
        • Ghaffar A.
        • Dujardin B.
        • et al.
        Access to medicines from a health system perspective.
        Health Policy Plan. 2013; 28: 692-704
        • Therapeutic Goods Administration
        Prescription medicines registration process: Department of Health.
        • Pharmaceutical Benefits Advisory Committee
        The Pharmaceutical Benefits Advisory Committee Guidelines: About the Guidelines.
        Department of Health, 2016 (Available from:)
        • Zhou B.
        • Carrillo-Larco R.M.
        • Danaei G.
        • Riley L.M.
        • Paciorek C.J.
        • Stevens G.A.
        • et al.
        Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants.
        Lancet. 2021; 398: 957-980
        • Schaffer A.L.
        • Pearson S.A.
        • Buckley N.A.
        How does prescribing for antihypertensive products stack up against guideline recommendations? An Australian population-based study (2006–2014).
        Br J Clin Pharmacol. 2016; 82: 1134-1145
        • Egan B.M.
        • Bandyopadhyay D.
        • Shaftman S.R.
        • Wagner C.S.
        • Zhao Y.
        • Yu-Isenberg K.S.
        Initial monotherapy and combination therapy and hypertension control the first year.
        Hypertension. 2012; 59: 1124-1131
        • Wang N.
        • Salam A.
        • Webster R.
        • de Silva A.
        • Guggilla R.
        • Stepien S.
        • et al.
        Association of low-dose triple combination therapy with therapeutic inertia and prescribing patterns in patients with hypertension: a secondary analysis of the TRIUMPH Trial.
        JAMA Cardiol. 2020; 5: 1219-1226
        • Gavino A.I.
        • Isaac V.
        • McLachlan C.S.
        Hypertension status and associations with self-rated health and general practitioner health seeking in a rural Australian cohort.
        J Cardiovasc Dev Dis. 2018; 5: 1-13
        • Webster R.D.
        • Castellano J.M.M.D.
        • Onuma O.K.M.D.
        Putting polypills into practice: challenges and lessons learned.
        Lancet. 2017; 389: 1066-1074
        • Therapeutic Goods Administration
        Medicine Shortages Information Initiative.
        Therapeutic Goods Administration, 2021
        • Therapeutic Goods Administration
        Australian Regulatory Guidelines for Advertising Therapeutic Goods (ARGATG) – Guidance for advertisers.
        • Clarke P.M.
        • Avery A.B.
        Evaluating the costs and benefits of using combination therapies.
        Med J Australia. 2014; 200: 518-520
        • Collier R.
        Drug patents: the evergreening problem.
        CMAJ. 2013; 185: E385-E386